This document discusses intrauterine devices (IUDs) including their history, types, advantages, and disadvantages. It describes the development of medicated IUDs including copper-bearing and hormone-releasing IUDs. Comparative efficacy data is presented showing progesterone-releasing IUDs are associated with less bleeding and cramping than copper IUDs. Newer IUD designs aim to provide long-acting contraception through controlled drug release over extended periods.

2. ⦿ Introduction
⦿ Introduction of IUDs
⦿ Intra Uterine Devices-
◾Types of IUDs
◾Advantages of IUDs
◾Disadvantages of IUDs
◾Design of IUDs
⦿ Development of medicated IUDs
◾Copper bearing IUDs
◾Hormone releasing IUDs
⦿ Comparative efficacy of medicated & non-
medicated IUDs
⦿ New development

3. INTRODUCTION
CONTRACEPTION:
• Contra-opposite/ prevent
• Ception- conception (union of male & female
gamates to reproduce new ones)
• It is the method or technique or process which
results into temporary or permanent loss of
capability to reproduce or conceive a young one.
⦿3 most popular methods of contraception:
 Oral contraceptive pills
 Condoms or diaphragms
 Intrauterine device

4. Pear shaped, thick-walled
muscular organ suspended in the
anterior wall of pelvic cavity.
Shape: triangular, flattened
antero-posteriorly.
Dimensions: (in normal state)
Length- 3 inches
Width- 2 inches
Parts-
 Fundus
Body (Uterine Cavity, Isthmus)
Cervix (Cervical canal, Internal Os,
External Os)
Openings-
Superior- fallopian tubes
Inferior- Vagina (mouth of
Uterus)

5. ⦿ Endometrium – inner coat of uterine wall made up of
simple columnar epithelium, areolar connective tissue &
endometrial glands.
◾Stratum Functionalis- innermost, sloughed off during
menstruation
◾Stratum Basalis- permanent, gives new s. functionalis.
⦿ Myometrium – Thick, muscular middle layer made up of
3 layers of smooth muscles (Middle thick circular &
other two longitudinal)
⦿ Peritoneum – External surface of uterus which attaches
uterus to pelvic cavity by ligaments

6. ⦿During reproductive ages nonpregnant woman
exihibit cyclic changes in ovaries & uterus, called
as Menstrual cycle.
⦿Typically of 28 days & divided into 4 phases-
 Menstrual Phase (5 days)
 Pre-ovulatory phase / Follicular phase (6-13 days)
 Ovulatory phase (on 14th day)
 Post-ovulatory phase / Leutial phase (14-28 days)

8. ⦿ DEFINITION
IUD’s are medicated devices intended to release a small quantity of drug
into uterus in a sustained manner over prolonged period of time.
⦿ NON MEDICATED:
Ring shaped iud’s made of stainless steel which haven used by 50
millions women in china .
Plastic IUDS :
Fabricated from polyethylene or polypropylene which are sold in
Asia, south Africa ,south America.
Lippes loop iud & Saf -T-coil is still available commercially in US.
⦿ MEDICATED:
Copper bearing IUD E.g. cu 7, CuT-380
Progesterone releasing IUDS e.g., Progestasert

9. ⦿1920- First generation IUD’s
◾ Constructed from silkworm gut & flexible metal wire
Eg. Grafenberg star & Ota ring
◾ Decline in popularity-
 Difficulty in insertion
 Need for frequent removal- pain & bleeding
 Other serious complications

10. ⦿Then-
◾ Several Plastic based IUD’s of varying sizes & shapes
were prepared using inert biocompatible polymers
like-
 Polyethylene
 Polypropylene
 Ethylene-vinyl acetate copolymers
 Silicon Elastomer

11. ⦿Modern Era- development of
◾ Margulies- Plastic spirals
◾ Lippes- Loop
◾ Dalkon shield IUD
⦿Efficacy of these IUD’s was proportional to their
surface area that is in direct contact with
endometrium.
⦿Larger IUD’s were more effective but expulsion
rate is high as these produce-
◾ Endometrial Compression
◾ Myocardial Distention
◾ Uterine cramps
◾ Bleeding

12. 18
 The device is made of T
shaped polyethylene plastic.
 This device uses copper wire
wound to the stem of T.
 Grades as per the surface
area of wire
• Cu-T-30,
• Cu-T-200,
• Cu-T-380.

13. ⦿ Cytotoxic, Spermatocidal & spermato-depressive action
⦿ Competitive inhibitor of steroid-receptor interaction.
Eg. Cupric ions –Potent inhibitor
 17 estradiol & Progesterone binding to their receptors.
 Progesterone receptors were more susceptible.
 Progestational proliferation severely inhibited.
⦿ Cu taken up by endometrial epithelium & stromata.
⦿ Cu conc. in uterine cytoplasm –1.4 x 10-6 M
⦿ Little effect on sperm mobility.

14. ⦿Continuous release by ionization & chelation process.
⦿Diameter of wire was reduce with time by corrosion
& flacking of metal
⦿Cu-7 284 deliver Cu at a rate of following expression-
Dosage (mg)=0.3 * month + 3.79
⦿Release 9.87 µg/day
⦿Linear relationship between cumulative copper
release with the duration
⦿Reduction in copper release due to formation of-
◾ Corrosion layer- of protein
◾ Encrustation layer- of calcium (impermeable)

15. Clinical effectiveness for 3- years use of Cu-T-200
Event Year 1 Year 2 Year 3
Pregnancies 2.6 2.5 3.6
Expulsions 7.3 2.3 2.5
Removals
Bleeding/ pain 8.7 7.3 5.2
other medical reasons 2.7 2.4 2.0
Planning pregnancy 1.9 4.4 7.0
Other medical reasons 2.3 3.4 7.9
Termination rates 25.5 22.3 28.3
Continuation rates 74.5 77.7 71.7
*Events per 100 women

16. ⦿Mfg by G.D. Searle & Co.
⦿First device approved by US- FDA for 3 yrs of
use.
⦿Polypropylene plastic device shaped like 7
⦿89 mg copper wire around vertical limb with
surface area of 200 sq. mm
⦿Release 9.87µg/day for 40 months
⦿Smaller volume (0.09 cm3) than Cu-T (0.16 cm3)
- easily inserted in nulliparous women.
⦿No need of cervical dilation
⦿Removal is painless.

18. ⦿ Efficacy improved when copper wire is located on the
transverse arm as in close contact with upper portion of
uterine cavity.
⦿ Cu-T-380A (US approval -1980)
◾Two collars of Cu on transverse arm
◾Each collar provides additional surface are of 30 sq. mm.
⦿ Cu-T-200C
◾Seven copper sleeves of Copper on both arms
◾Efficious same as Cu-T-380A
◾Retain physical integrity for 15-20 yrs.
◾Long acting- beneficial to population in which medical
care not readily available.

19. ⦿ Multiload Cu IUD: MLCu-250
◾ Combination of Cu-T & Dalkon Shield without central plastic
membrane.
◾ Blunt apex of device fits in to vault of uterine cavity without
penetrating endometrial walls
◾ Two teeth-studded side arms adapt to the contours of the uterine
cavity
◾ During uterine contraction Fundus presses against upper edge of
IUD, results in bending of arms.
◾ Pregnancy rate- 0.3% only
◾ Expulsion- 1% only
⦿ Other Devices-
◾ MLCu-250,
◾ MLCu-325
◾ MLCu-250 mini

20. ⦿ Use of hormone in IUD- initiated by Doyle & Clewe
⦿ Then Croxatto et al showed that a progestin released
at a controlled rate from a silicone capsule inserted in
rabbit uterine cavity, prevent implantation.
⦿ 1970- Scommegna & coworkers affix progesterone
containing silicone capsules to modified Lippes loop.
Granted US-patent.
⦿ Early models had high expulsion rates or side effects.
⦿ T-shaped progesterone releasing IUD were
developed, improvement in efficacy.
⦿ Release rate of 65 µg/day was found to produce
contraception & selected as final design of IUD.

21. ⦿ Secretion of secretary phase is hormonally controlled
◾Optimum amt. of estrogen & progesterone required for
proper development.
⦿ Implantation of blastocyst takes place on secretary
endometrium.
⦿ Decidual reaction- after implantation
◾Stromal cells enlarge & grow as polyhedral cells rich in
glycogen & lipids. These changes takes place in presence
of implanted blastocysts.
⦿ Once decidual reaction occurred, implantation of
blastocyst cannot takes place again.
⦿ Endometrial hyper-maturation is unfavorable for
implantation.
⦿ Maturation of endometrium is associated with decidual
formation which is induced by Progesterone.

22. ⦿Membrane Controlled Reservoir type D.D.Ds-
Polymeric membrane encapsulates the drug &
also controls the release.
◾Two types
 Single Component System
 Multiple Component System
Cont.

23. ⦿Single Component System
◾Drug in solid form encapsulated in capsule of
biocompatible polymeric material
◾Polymer- Silicone elastomer / Polyethylene
◾E.g. Scommegna’s silicone-based IUD
◾Drug release- zero order kinetics
◾Silicone elastomer widely used previously as
polymer- do not posses required tensile
strength or elastic modulus.
◾To overcome drawbacks- copolymers of
Poly(dimethylsiloxone) with polycarbonate or
polyurethane were prepared.
Cont.

24. ⦿ Multi component System-
◾Encapsulation of liquid medium saturated
with excess of drug in rate
controlling polymeric membrane.
E. g. Progestasert (Alza Corp.)
 Membrane- Ethylene vinyl acetate
copolymer
 38 mg of Progesterone suspended in
silicone oil
 Release at constant rate of 65 µg/day
 Zero order release rate till drug solution
become unsaturated
 60% of loading dose in reservoir
compartment depleted during first year.
 Useful life is 1 yr.

25. ⦿Polymer-matrix Diffusion-Controlled D.D.Ds-
Homogenously dispersing drug particles in a cross
linked polymeric matrix
◾Two types
 Retrievable Matrix Device
 Biodegradable Matrix Device

26. ⦿ Retrievable Matrix Device-
◾Retrieved or removed after termination of
treatment
◾Preparation-
1) Mix drug powder with a semisolid silicone
elastomer  vulcanization at room / low temp.
2) Mix drug powder with low density polyethylene
particles  Melt & extrude
◾Drug release is linearly proportional to square root
of time
Cont.

27. ⦿Biodegradable matrix device:
◾No need of retrieving at the termination of treatment.
◾Preparation –
Dissolve drug + Biodegradable polymer e.g.
Poly(lactic acid)  in common organic solvent 
Melt pressing at elevated temp. after flashing off
solvent
◾Drug release is combination of polymer hydrolysis &
drug diffusion

28. ⦿Sandwich-type D.D.D.
◾Hybrid of polymer membrane permeation with
polymer matrix diffusion
◾Thin rate controlling membrane encapsulates a
high permeable drug dispersing matrix.
◾Release rate can be improved by coating porous
support with silicone elastomer.
◾E.g. Nova-T (Leiras Pharmaceuticals, Finland)
 Drug Levonorgesterel (more potent progesterone analog)
 T shaped polyethylene support by a sandwich type silicone
based drug reservoir
 Daily release – 20 µg
 Lifetime- more than 5 yrs.

29. ⦿Estriole Releasing IUD’s
◾Synthesis of estradiole dependant
uterine RNA is essential for
implantation
◾Estriole binds with uterine
receptors & compete with
estradiole. But incapable of
inducing uterine growth.
◾It interfere with synthesis of
estradiole induced uterine RNA,
preventing implantation.
◾Release rate of 1.25 µg/day
effectively inhibits development &
implantation of blastocyst.

30.  Use of Cu -7 group was declined due to the problem
of excessive bleeding .
 Irregular bleeding was higher in Cu – 7 group
(13.4%) than in progestasert group (7.5%).
 But progestasert has a limited life span of one year
which is disadvantageous as compared to three
year users life of Cu -7.
.

31. Changes in enzymatic activity-
 Copper bearing IUD produce significant variations in
secretary phase of the endometrium with two fold
increase in total enzyme activity.
 Progesterone releasing IUD induced no (or only small )
change in activity of lysosomal enzymes and increased
the stability of lysosomal membrane during secretary
phase.
 The changes in activities and sub cellular distribution
of lysosomal enzymes induced by non medicated
placebo IUD were found to be quantitatively small and
of limited biological significance .
.

32. Changes in endometrium-
 The plain and copper bearing spring coil IUDs the cyclic
patterns of endometrium was preserved .
 Progesterone releasing IUDs produce the histological
changes that made endometrium unsuitable for
implantation .
 Mestranol releasing device produces proliferative or
hyperplastic changes in both glandular & stromal cells
with prevention of secreatory changes in endometrium
which become unreceptive to ova
.

33. Changes in menstrual bleeding-
 Insertion of copper bearing IUDs has resulted in
increased in menstrual blood loss and decreased in Hb
compared to pre insertion cycle
 Insertion of progesterone releasing IUDs yielded either
no change or reduction in menstrual blood loss & no
significant variation in Hb conc.

34.  The copper IUD prevents ectopic pregnancies.
 This contraceptive is very cost effective
(inexpensive) over time.
 Use of an IUD is convenient, safe & private.
 The IUD may be inserted immediately following
the delivery of a baby or immediately after an
abortion.
 Some studies of IUDs have shown a decreased
risk for uterine cancer. There is also some
evidence that IUDs protect against cervical
cancer.

35. ⦿ There may be cramping, pain after insertion.
⦿ The number of bleeding days is slightly higher than
normal
⦿ Somewhat increased menstrual cramping.
⦿ If bleeding pattern is bothersome, contact the doctor.
⦿ The IUD provides no protection against sexually
transmitted infections.
⦿ There is a higher initial cost of insertion. However, after 2
years, it is the most cost-effective contraceptive method.
⦿ The IUD must be inserted by a doctor, nurse or physician’s
assistant.